The breeding of domestic dogs for dog fighting has resulted in numerous genetic alterations in a breed widely acknowledged to be the most successful fighting dog: the American Pit Bull Terrier (APBT). Much of the genetic foundation underlying the motivation and ability for pit fighting can be traced back to the earliest use of dogs for hunting purposes and continued through the selective breeding for use of dogs in wars and bull and bear baiting. In the development of the APBT as a fighting dog, there were two main breeding criteria. The first was, and remains, fighting success. The trait most prized by breeders of fighting dogs and considered most contributory to fighting success is ‘gameness’, which is the perseverance at a task even under extreme adversity, such as injury, pain, or fatigue. The second criterion was the absence of human-directed aggression. Since dogs are handled extensively before, during, and after the fights, dogs that showed aggression toward humans were eliminated from the gene pool. Indeed, anecdotal reports suggest that breeding may have been carried beyond that of simply selecting against human aggressiveness to a degree of enhanced affinity for humans. The result is that today's fight-bred APBT is genetically predisposed — but not predestined — to aggressiveness toward other dogs and a strong social attraction to humans. The human affinity trait is a highly valuable characteristic that ought to be preserved. With the appropriate breeding decisions, the power of genetic selection suggests that this goal, along with normalising the genetic disposition for conspecific aggressive tendencies, should be ultimately achievable.